Blast-induced Traumatic brain injury (bTBI) has become the "signature injury" of Operations Iraqi/Enduring Freedom (OIF/OEF) and is also increasingly frequent in civilians as a result of industrial and terrorist explosions. The mechanisms by which blast shockwaves contribute to bTBI is being investigated using both large and small animal models. Small animal models of bTBI predominantly utilize compressed air-driven shock tubes to generate an injury, while large animal models employ chemical explosives (i.e., RDX - the main explosive component of C-4 plastic explosives) in both open-air and a variety of enclosed spaces. The differences in model design and shockwave source make comparison of results from each model difficult. Previous bTBI studies have focused on the relationship between peak blast pressure and brain injury. However, we hypothesize that other components of the shock wave may also contribute to the brain injury. In an effort to determine which components of the blast contribute to the injury, we developed and characterized the McMillan Blast Device (MBD), a shock tube that can utilize compressed gas (air, helium) or chemical explosives (RDX, oxyhydrogen) as the shockwave source. Shockwaves produced from compressed gas sources differ substantially from those produced by chemical explosives within the MBD. This proposal seeks to determine which components of the shock wave contribute to brain pathology in rats. The overall hypothesis of this proposal is that positive phase duration, in addition to peak overpressure, plays a role in the injury produced by blasts. To examine this hypothesis, Aim 1 will compare blasts of similar peak overpressures produced by oxhydrogen and compressed air. The oxyhydrogen-driven blasts have a shorter positive phase duration and are therefore anticipated to produce less brain injury. This will be evaluated using a range of peak overpressures. Brain injury will be assessed using markers diffuse axonal injury (DAI), blood-brain barrier (BBB) compromise, oxidative stress and neuron death. Aim 2 will expand upon Aim 1 by shortening the positive phase duration of a compressed air-driven shockwave to a length comparable to oxyhydrogen-driven blasts and comparing resultant brain injury. Aim 3 will examine the hypothesis that reflection of the blast waves, which extends the duration of the overpressure phase, will exacerbate the extent of brain injury produced by a blast. PUBLIC HEALTH RELEVANCE: Blast-induced traumatic brain injury (bTBI) is becoming more prevalent among military and civilian populations, while the mechanisms underlying the pathologic mechanisms associated with bTBI remain largely unknown. This proposal will evaluate components of the blast wave that contribute to brain injury by using both compressed gas and chemical explosive sources for the blast wave. These results will aid in the design of protective structures and personal protective gear to mitigate the effects of blast wave components which contribute to bTBI.